A Study on the Impact of Bivalirudin Usage During PCI for High-risk Plaques on Post-PCI Coronary Microcirculation.

Phase 4

Recruiting

• Conditions: Coronary Microvascular Dysfunction
• Interventions: Drug: standard heparin; Drug: Bivalirudin

• Registration Number: NCT05984537
• Lead Sponsor: Peking University First Hospital

Brief Summary

In this study, investigators enrolled patients with coronary heart disease who were scheduled to undergo percutaneous coronary intervention (PCI) and had high-risk plaques according to computed tomography angiography (CTA). During the PCI procedure, patients will be randomly assigned to receive either bivalirudin or standard heparin anticoagulation therapy. Investigators will compare the post-PCI coronary angiography-derived index of microcirculatory resistance (CaIMR), thrombolysis in myocardial infarction (TIMI) blood flow grade, CTFC (corrected TIMI frame count), TIMI myocardial perfusion grading(TMPG), levels of troponin, and major adverse cardiac events (MACE) during a follow-up period of 6 months between the two groups. Investigators aim to explore the potential benefits of bivalirudin perioperative anticoagulation therapy in improving coronary microvascular dysfunction (CMD) after PCI for high-risk plaques in coronary artery lesions.

Detailed Description

Coronary artery disease (CAD) is one of the leading causes of death in China, with nearly 11.39 million patients affected. Percutaneous coronary intervention (PCI) is an important treatment for CAD, but despite effectively improving coronary stenosis, patients still experience the phenomenon of no-reflow (NR), which seriously affects long-term prognosis. Coronary microvascular dysfunction (CMD) during PCI is an important mechanism of NR, and previous studies have shown that immediate post-PCI CMD significantly affects long-term prognosis. Previous studies have shown that high-risk plaques identified by computed tomography angiography (CTA) before surgery in patients with stable coronary heart disease are closely related to the occurrence of NR and can serve as a predictor of NR after PCI. Therefore, CTA can identify high-risk patients for NR before PCI and has clinical value in preventing NR. Bivalirudin is a direct thrombin inhibitor that can block the continued development of blood clots. BIVAL study has shown that bivalirudin can improve post-PCI microcirculation dysfunction in patients with acute ST-segment elevation myocardial infarction, and animal experiments have shown that bivalirudin can improve thrombin-induced endothelial hyperpermeability.

In this study, investigators plan to identify high-risk coronary artery plaques early through CTA examination. Participants will be randomly assigned to receive either bivalirudin or standard heparin anticoagulation therapy. Investigators will compare the post-PCI CaIMR, thrombolysis in myocardial infarction (TIMI) blood flow grade, CTFC (corrected TIMI frame count), TIMI myocardial perfusion grading(TMPG), levels of troponin, and major adverse cardiac events (MACE) during a follow-up period of 6 months between the two groups. Investigators will also explore the possible mechanisms by which bivalirudin reduces coronary microcirculatory injury and improves endothelial function through the detection of endothelial function-related biomarkers, providing evidence for the multi-effectiveness of bivalirudin in myocardial protection.

Study Timeline

• Study Start: 2023-07-01
• Study First Submitted: 2023-07-23
• Study First Submitted QC: 2023-08-01
• Study First Posted: 2023-08-09
• Status Verified: 2024-04
• Last Update Submitted: 2024-04-01
• Last Update Posted: 2024-04-02
• Primary Completion: 2025-03-01
• Study Completion: 2025-03-04

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 70

Inclusion Criteria

1. aged 18 years or older;
2. diagnosed with non-ST-segment elevation myocardial infarction or unstable angina pectoris;
3. scheduled to undergo elective coronary angiography and intervention;
4. coronary computed tomography angiography showing high-risk plaque features within 3 months prior to the procedure;
5. voluntary participation in the study and signed informed consent.

Exclusion Criteria

1. prior PCI of the target vessel within 3 months;
2. cardiogenic shock, active bleeding, bleeding disorders, irreversible coagulation dysfunction, severe liver dysfunction (Child-Pugh class C), severe renal dysfunction (eGFR < 30 ml/min/1.73m2), and dependence on dialysis;
3. life expectancy less than 1 year;
4. chronic total occlusion of the target vessel;
5. poor opacification of the target vessel, severe vessel overlap or distortion, and inability to completely expose the lesion site;
6. allergy to contrast agents, verapamil, or its excipients;
7. severe uncontrolled hypertension (systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 100 mmHg);
8. subacute bacterial endocarditis.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
standard heparin group	standard heparin	participants using standard heparin during PCI
bivalirudin group	Bivalirudin	participants using bivalirudin during PCI

Primary Outcome Measures

Name	Time	Method
CaIMR	3 days	The caIMR value of the target vessel immediately after PCI.
CMD	3 days	The proportion of target vessels with caIMR ≥ 25 and caIMR ≥ 40 immediately after PCI.

Secondary Outcome Measures

Name	Time	Method
biomarker_myocardial injury markers	3 days	Peak levels of myocardial injury markers (CK-MB and CTNI) after PCI.
biomarker_eNOs	3 days	Serum levels of eNOs after PCI.
clinical events	6 months	(1) MACE (including cardiac death, target vessel revascularization, target vessel myocardial infarction, and heart failure readmission) at 30 days and 6 months after PCI; (2) Major adverse events (including all-cause death, non-fatal myocardial infarction, unplanned revascularization, definite or probable stent thrombosis, and clinically significant bleeding events) at 30 days and 6 months.
biomarker_ET-1	3 days	Serum levels of ET-1 after PCI.
imaging examination_microcirculation	3 days	Other indicators for assessing microcirculation during the procedure (including TMPG, TIMI frame count, and myocardial staining grade).
imaging examination_longitudinal myocardial strain	3 days	Changes in global longitudinal myocardial strain of the left ventricle measured by post-PCI echocardiography compared to baseline values.

Trial Locations

Locations (1)

Peking university first hospital; 🇨🇳 Beijing, Beijing, China